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Aurora kinase A inhibition and paclitaxel as targeted combination therapy for head and neck squamous cell carcinoma

Abhijit Mazumdar1, Ying C Henderson, Adel K El-Naggar

  • 1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Head & Neck
|December 25, 2008
PubMed
Abstract

Insights

Aurora kinase A (AURKA) is overexpressed in head and neck squamous cell carcinoma (HNSCC). Inhibiting AURKA induces apoptosis and suppresses HNSCC cell proliferation, suggesting AURKA as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Aurora kinase A (AURKA) is frequently amplified in various human cancers.
  • Head and neck squamous cell carcinoma (HNSCC) incidence of AURKA amplification varies.
  • Investigating AURKA as a potential therapeutic target in HNSCC.

Purpose of the Study:

  • To determine the role of AURKA in HNSCC.
  • To evaluate AURKA as a therapeutic target for HNSCC.

Main Methods:

  • Immunohistochemical analysis of AURKA expression in 63 paired normal and tumor HNSCC samples.
  • AURKA inhibition using siRNA in HNSCC cells, assessed by RT-PCR and Western blot.
  • Cell proliferation (MTT assay) and cell cycle distribution (flow cytometry) analysis of siRNA-treated HNSCC cells, with and without paclitaxel.

Main Results:

  • AURKA expression was elevated in 85% of HNSCC tumors compared to adjacent normal tissues.
  • High AURKA expression and kinase activity were observed in HNSCC cells and primary tumors.
  • AURKA inhibition induced apoptosis and suppressed HNSCC cell proliferation.
  • Combination of AURKA inhibition and paclitaxel synergistically enhanced apoptosis.

Conclusions:

  • AURKA represents a promising therapeutic target for HNSCC.
  • Further research into small-molecule AURKA inhibitors for HNSCC treatment is recommended.

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